Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial
Abstract Gamma-amino butyric acid (GABA) has in experimental studies been found to promote beta-cell proliferation, enhance insulin secretion and reduce inflammation, positioning it as a candidate drug for type 1 diabetes (T1D) therapy. This phase I/II randomized controlled trial assessed the safety...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-95751-y |
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| author | Henrik Hill Per Lundkvist Georgios Tsatsaris Bryndis Birnir Daniel Espes Per-Ola Carlsson |
| author_facet | Henrik Hill Per Lundkvist Georgios Tsatsaris Bryndis Birnir Daniel Espes Per-Ola Carlsson |
| author_sort | Henrik Hill |
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| description | Abstract Gamma-amino butyric acid (GABA) has in experimental studies been found to promote beta-cell proliferation, enhance insulin secretion and reduce inflammation, positioning it as a candidate drug for type 1 diabetes (T1D) therapy. This phase I/II randomized controlled trial assessed the safety and efficacy of long-term treatment with Remygen® (Diamyd Medical), a controlled-release oral GABA formulation, as a potential beta-cell regenerative therapy in adults with long-standing T1D. Thirty-five male subjects with T1D (≥ 5 years) were randomized into three arms receiving the study drug(s) once daily for 6 months: GABA 200 mg (Arm 1), GABA 600 mg (Arm 2) and GABA 600 mg + alprazolam 0.5 mg for 3 months followed by GABA 600 mg alone for 3 months (Arm 3). Safety measures, hormonal counter-regulation during hypoglycemic clamps, fasting- and stimulated C-peptide levels, were assessed at multiple timepoints. Safety concerns included elevated aspartate aminotransferase (AST) in nine subjects, leading to the withdrawal of two subjects. Most elevations were, however, transient with no dose-differences. No effects were observed on fasting- or stimulated C-peptide levels, CGM metrics or HbA1c. Hypoglycemic hormonal counter-regulation was unaltered. To conclude, we found no clinical evidence of a beta-cell regenerative effect of GABA, but side effects were commonly observed. |
| format | Article |
| id | doaj-art-58a9e93c0d4448dc97e89b2386f7b33f |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-58a9e93c0d4448dc97e89b2386f7b33f2025-08-20T03:04:58ZengNature PortfolioScientific Reports2045-23222025-04-0115111210.1038/s41598-025-95751-yLong-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trialHenrik Hill0Per Lundkvist1Georgios Tsatsaris2Bryndis Birnir3Daniel Espes4Per-Ola Carlsson5Department of Women’s and Children’s Health, Uppsala UniversityDepartment of Medical Sciences, Uppsala UniversityDepartment of Medical Sciences, Uppsala UniversityDepartment of Medical Cell Biology, Uppsala UniversityDepartment of Medical Sciences, Uppsala UniversityDepartment of Medical Sciences, Uppsala UniversityAbstract Gamma-amino butyric acid (GABA) has in experimental studies been found to promote beta-cell proliferation, enhance insulin secretion and reduce inflammation, positioning it as a candidate drug for type 1 diabetes (T1D) therapy. This phase I/II randomized controlled trial assessed the safety and efficacy of long-term treatment with Remygen® (Diamyd Medical), a controlled-release oral GABA formulation, as a potential beta-cell regenerative therapy in adults with long-standing T1D. Thirty-five male subjects with T1D (≥ 5 years) were randomized into three arms receiving the study drug(s) once daily for 6 months: GABA 200 mg (Arm 1), GABA 600 mg (Arm 2) and GABA 600 mg + alprazolam 0.5 mg for 3 months followed by GABA 600 mg alone for 3 months (Arm 3). Safety measures, hormonal counter-regulation during hypoglycemic clamps, fasting- and stimulated C-peptide levels, were assessed at multiple timepoints. Safety concerns included elevated aspartate aminotransferase (AST) in nine subjects, leading to the withdrawal of two subjects. Most elevations were, however, transient with no dose-differences. No effects were observed on fasting- or stimulated C-peptide levels, CGM metrics or HbA1c. Hypoglycemic hormonal counter-regulation was unaltered. To conclude, we found no clinical evidence of a beta-cell regenerative effect of GABA, but side effects were commonly observed.https://doi.org/10.1038/s41598-025-95751-yType 1 diabetesGABABeta-CellOral therapyRegenerative therapy |
| spellingShingle | Henrik Hill Per Lundkvist Georgios Tsatsaris Bryndis Birnir Daniel Espes Per-Ola Carlsson Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial Scientific Reports Type 1 diabetes GABA Beta-Cell Oral therapy Regenerative therapy |
| title | Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial |
| title_full | Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial |
| title_fullStr | Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial |
| title_full_unstemmed | Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial |
| title_short | Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial |
| title_sort | long term gamma aminobutyric acid gaba treatment fails to regain beta cell function in longstanding type 1 diabetes in a randomized trial |
| topic | Type 1 diabetes GABA Beta-Cell Oral therapy Regenerative therapy |
| url | https://doi.org/10.1038/s41598-025-95751-y |
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